Evidence that COMT genotype and proline interact on negative-symptom outcomes in schizophrenia and bipolar disorder.
Evidence that COMT genotype and proline interact on negative-symptom outcomes in schizophrenia and bipolar disorder.
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DOI：
10.1038/tp.2016.157
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发表时间：
2016-09-13
影响因子：
6.8
通讯作者：
Clelland JD
中科院分区：
文献类型：
--
作者：
Clelland CL;Drouet V;Rilett KC;Smeed JA;Nadrich RH;Rajparia A;Read LL;Clelland JD
外周脯氨酸升高与精神疾病有关，有证据表明脯氨酸是一种神经调节剂。脯氨酸脱氢酶 (PRODH) 基因编码催化脯氨酸分解代谢的酶，定位于人类染色体 22q11.2，该区域会导致精神分裂症的风险。在 Prodh 缺失小鼠中，外周脯氨酸升高与另一个 22q11.2 基因儿茶酚-O-甲基转移酶 (COMT) 之间对神经传递和行为的相互作用已被报道。我们探讨了精神分裂症患者的空腹血浆脯氨酸水平和 COMT Val158Met 基因型与症状（阳性、阴性和总症状）之间的关系。在一项探索性研究中，我们还检查了双相情感障碍患者的症状变化。外周脯氨酸和 COMT 对精神分裂症阴性症状有显着的相互作用（P<0.0001，n=95）。在 COMT Val/Val 患者中，高脯氨酸与低阴性症状评估量表 (SANS) 评分相关。相反，在携带 Met 等位基因的患者中，高脯氨酸与高 SANS 评分相关。脯氨酸和 COMT 之间的关系似乎也可以改变精神疾病的阴性症状。在双相情感障碍中，阴性症状变化也观察到显着的相互作用（P=0.007，n=43）。阴性症状很棘手，目前的药物基本上无法解决。这些数据表明外周脯氨酸和 COMT 基因型之间存在显着的相互作用，影响精神分裂症和双相情感障碍的阴性症状。高脯氨酸对 COMT 基因型的症状有相反的影响，可能对治疗决策有影响。
Elevated peripheral proline is associated with psychiatric disorders, and there is evidence that proline is a neuromodulator. The proline dehydrogenase (PRODH) gene, which encodes the enzyme that catalyzes proline catabolism, maps to human chromosome 22q11.2, a region conferring risk of schizophrenia. In the Prodh-null mouse, an interaction between elevated peripheral proline and another 22q11.2 gene, catechol-O-methyltransferase (COMT), on neurotransmission and behavior has been reported. We explored the relationship between fasting plasma proline levels and COMT Val158Met genotype on symptoms (positive, negative and total) in schizophrenia patients. In an exploratory study we also examined symptom change in patients with bipolar disorder. There was a significant interaction between peripheral proline and COMT on negative symptoms in schizophrenia (P<0.0001, n=95). In COMT Val/Val patients, high proline was associated with low Scale for the Assessment of Negative Symptom (SANS) scores. In contrast, high proline was associated with high SANS scores in patients carrying a Met allele. The relationship between proline and COMT also appears to modify negative symptoms across psychiatric illness. In bipolar disorder, a significant interaction was also observed on negative-symptom change (P=0.007, n=43). Negative symptoms are intractable and largely unaddressed by current medications. These data indicate a significant interaction between peripheral proline and COMT genotype, influencing negative symptoms in schizophrenia and bipolar disorder. That high proline has converse effects on symptoms by COMT genotype, may have implications for therapeutic decisions.
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